News and outreach
scientific advancesBack
A study explores the key role of the SIN-3 protein in the regulation of gene expression
published on 29/07/2024
Using the nematode C. elegans as a model organism, researchers from the CABD reveal the importance of SIN-3 in the regulation of mitochondrial and nuclear gene expression, which is vital for cellular energy production.
Mitochondria are essential for the functioning of cells, as they are responsible, among other things, for cellular respiration, i.e. they are the ones that carry out the process of oxidizing food molecules to produce the energy needed by the cell.
This essential process is carried out thanks to the formation of sophisticated protein complexes in the inner membrane of the mitochondrion. Most of the proteins that form the respiratory chain are encoded in the nuclear DNA and are transported to the mitochondria, but 13 of them are encoded in the mitochondrial DNA. Thus, cellular respiration depends on the coordinated expression of the mitochondrial and nuclear genomes to assemble the respiratory chain complexes.
What can cause an imbalance in the the proportions of these proteins? And what are the consequences if these protein complexes are not assembled? Researchers at the CABDMarta Artal Sanz and María Jesús Rodríguez Palero, professors at the Universidad Pablo de Olavide, in collaboration with the laboratory of Francesca Palladino (Ecole Normale Supérieure de Lyon), have focused their study on the mutation of the SIN-3 protein, a regulator of gene transcription, and its critical role in transcription regulator, and also in both the nucleus and mitochondria of cells.
The research, performed for the first time in a whole organism, in this case in the nematode C. elegans, demonstrated that the SIN-3 mutation causes a dysregulation of gene expression. In particular, an increase in the expression of genes encoded in the mitochondrial genome and a decrease in mitochondrial genes encoded in the nucleus were observed, an imbalance that resulted in mitochondrial fragmentation, alterations in oxygen consumption and accumulation of polyamines.
SIN-3 loss in C. elegans leads to a misregulation of mitochondrial fragmentation and altered respiration. Sin-3 mutants also display reduced levels of SAM and
accumulation of polyamines / Ilustration: Liesbeth de Jong.
This finding is relevant because the SIN3 protein is conserved throughout evolution and its lack or malfunction is implicated in some types of autism. In addition, its involvement in mitochondrial metabolism suggests a possible connection with the development of certain types of cancer.
The research advances the understanding of how the regulation of gene transcription affects mitochondrial function, underscoring the need for a precise balance for the correct assembly of protein complexes essential for cellular respiration. Furthermore, it could open new avenues for the understanding and treatment of diseases related to mitochondrial dysfunction and gene regulation.
The article:
Giovannetti M, Rodríguez-Palero M.-J., Fabrizio P.,..., Artal-Sanz M., Palladino F. Sin-3 Transcriptional coregulator maintains mitochondrial homeostasis and pplyamine flux iScience 2024 https://doi.org/10.1016/j.isci.2024.109789
This press release was prepared with 'unidad técnica de comunicación de la UPO'.
